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Concentration-Responsive Gd-DOTA Nanomicelles via Chain-Length Engineering for Transporter-Independent Hepatobiliary
Youli Zhang1,2, Lulu Wang1, Yanmin Zheng1
1High Magnetic Field Laboratory, Hefei Institute of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China.
Langmuir : the ACS Journal of Surfaces and Colloids
|April 21, 2026
Summary
We developed a novel gadolinium-based contrast agent (Gd-C12) that self-assembles for imaging and disassembles for clearance. This nanomedicine offers enhanced liver imaging and rapid, safe elimination from the body.
Area of Science:
- Nanomedicine
- Supramolecular Chemistry
- Biomedical Imaging
Background:
- Designing nanomedicines requires balancing stability for function with clearance for safety.
- Gadolinium-based contrast agents face challenges in long-term retention and clearance pathways.
Purpose of the Study:
- To develop a concentration-responsive gadolinium-based contrast agent using a "assemble-for-uptake, disassemble-for-clearance" strategy.
- To optimize agent properties by tuning alkyl chain length for controlled self-assembly and disassembly.
Main Methods:
- Rational molecular engineering of a single-component Gd-DOTA amphiphile.
- Tuning critical micelle concentration (CMC) via alkyl chain length.
- Characterization of nanomicelle properties (size, stability, T1 contrast) and in vivo evaluation of hepatic uptake and clearance.
Main Results:
- Identified Gd-C12 as the optimal agent, forming stable nanomicelles (38.6 ± 8.3 nm) with excellent T1 contrast.
- Gd-C12 demonstrated potent, transporter-independent hepatic enhancement (120% increase) via MPS recognition.
- Achieved rapid systemic clearance (>97%) due to spontaneous disassembly upon physiological dilution.
Conclusions:
- Gd-C12 represents a high-performance, transporter-independent contrast agent bridging nanomedicine and small molecule properties.
- This strategy enables reliable hepatic parenchymal enhancement irrespective of OATP expression levels.
- The "assemble-for-uptake, disassemble-for-clearance" approach effectively addresses nanomedicine stability and clearance challenges.
